scholarly journals Immune-Checkpoint Blockade Therapy in Lymphoma

2020 ◽  
Vol 21 (15) ◽  
pp. 5456 ◽  
Author(s):  
Ayumi Kuzume ◽  
SungGi Chi ◽  
Nobuhiko Yamauchi ◽  
Yosuke Minami
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Malignant Lymphoma ◽  
Hodgkin Lymphoma ◽  
Immune Checkpoint ◽  
Immune Cell ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Host Immune System ◽  
Cell Death Protein

Tumor cells use immune-checkpoint pathways to evade the host immune system and suppress immune cell function. These cells express programmed cell-death protein 1 ligand 1 (PD-L1)/PD-L2, which bind to the programmed cell-death protein 1 (PD-1) present on cytotoxic T cells, trigger inhibitory signaling, and reduce cytotoxicity and T-cell exhaustion. Immune-checkpoint blockade can inhibit this signal and may serve as an effective therapeutic strategy in patients with solid tumors. Several trials have been conducted on immune-checkpoint inhibitor therapy in patients with malignant lymphoma and their efficacy has been reported. For example, in Hodgkin lymphoma, immune-checkpoint blockade has resulted in response rates of 65% to 75%. However, in non-Hodgkin lymphoma, the response rate to immune-checkpoint blockade was lower. In this review, we evaluate the biology of immune-checkpoint inhibition and the current data on its efficacy in malignant lymphoma, and identify the cases in which the treatment was more effective.

scholarly journals Biomarkers for Response to Immune Checkpoint Blockade

2020 ◽  
Vol 4 (1) ◽  
pp. 331-351
Author(s):  
Shridar Ganesan ◽  
Janice Mehnert
Keyword(s):  
Immune Checkpoint ◽  
Immune Cell ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Clinical Activity ◽  
Host Immune System ◽  
Mutation Burden ◽  
Life Threatening ◽  
Expression Evaluation ◽  
Distinct Features

Immune checkpoint blockade (ICB) has significant clinical activity in diverse cancer classes and can induce durable remissions in even refractory advanced disease. However, only a minority of cancer patients treated with ICB have long-term benefits, and ICB treatment is associated with significant, potentially life-threatening, autoimmune side effects. There is a great need to develop biomarkers of response to guide patient selection to maximize the chance of benefit and prevent unnecessary toxicity, and current biomarkers do not have optimal positive or negative predictive value. A variety of potential biomarkers are currently being developed, including those based on assessment of checkpoint protein expression, evaluation of tumor-intrinsic features including mutation burden and viral infection, evaluation of features of the tumor immune microenvironment including nature of immune cell infiltration, and features of the host such as composition of the gut microbiome. Better understanding of the underlying fundamental mechanisms of immune response and resistance to ICB, along with the use of complementary assays that interrogate distinct features of the tumor, the tumor microenvironment, and host immune system, will allow more precise use of these therapies to optimize patient outcomes.

scholarly journals The Role of Immune Checkpoint Blockade in the Hepatocellular Carcinoma: A Review of Clinical Trials

2021 ◽  
Vol 11 ◽  
Author(s):  
Muhammet Ozer ◽  
Andrew George ◽  
Suleyman Yasin Goksu ◽  
Thomas J. George ◽  
Ilyas Sahin
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trials ◽  
Cell Death ◽  
Liver Cancer ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Primary Liver Cancer ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Line Treatment

The prevalence of primary liver cancer is rapidly rising all around the world. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Unfortunately, the traditional treatment methods to cure HCC showed poor efficacy in patients who are not candidates for liver transplantation. Until recently, tyrosine kinase inhibitors (TKIs) were the front-line treatment for unresectable liver cancer. However, rapidly emerging new data has drastically changed the landscape of HCC treatment. The combination treatment of atezolizumab plus bevacizumab (immunotherapy plus anti-VEGF) was shown to provide superior outcomes and has become the new standard first-line treatment for unresectable or metastatic HCC. Currently, ongoing clinical trials with immune checkpoint blockade (ICB) have focused on assessing the benefit of antibodies against programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte- associated antigen 4 (CTLA-4) as monotherapies or combination therapies in patients with HCC. In this review, we briefly discuss the mechanisms underlying various novel immune checkpoint blockade therapies and combination modalities along with recent/ongoing clinical trials which may generate innovative new treatment approaches with potential new FDA approvals for HCC treatment in the near future.

Enhancing KDM5A and TLR activity improves the response to immune checkpoint blockade

2020 ◽  
Vol 12 (560) ◽  
pp. eaax2282 ◽  
Author(s):  
Liangliang Wang ◽  
Yan Gao ◽  
Gao Zhang ◽  
Dan Li ◽  
Zhenda Wang ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
T Cell Activation ◽  
Immune Checkpoint ◽  
Cell Activation ◽  
Gene Signature ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Tensin Homolog ◽  
Cancer Models

Immune checkpoint blockade (ICB) therapies are now established as first-line treatments for multiple cancers, but many patients do not derive long-term benefit from ICB. Here, we report that increased amounts of histone 3 lysine 4 demethylase KDM5A in tumors markedly improved response to the treatment with the programmed cell death protein 1 (PD-1) antibody in mouse cancer models. In a screen for molecules that increased KDM5A abundance, we identified one (D18) that increased the efficacy of various ICB agents in three murine cancer models when used as a combination therapy. D18 potentiated ICB efficacy through two orthogonal mechanisms: (i) increasing KDM5A abundance, which suppressed expression of the gene PTEN (encoding phosphatase and tensin homolog) and increased programmed cell death ligand 1 abundance through a pathway involving PI3K-AKT-S6K1, and (ii) activating Toll-like receptors 7 and 8 (TLR7/8) signaling pathways. Combination treatment increased T cell activation and expansion, CD103+ tumor-infiltrating dendritic cells, and tumor-associated M1 macrophages, ultimately enhancing the overall recruitment of activated CD8+ T cells to tumors. In patients with melanoma, a high KDM5A gene signature correlated with KDM5A expression and could potentially serve as a marker of response to anti–PD-1 immunotherapy. Furthermore, our results indicated that bifunctional agents that enhance both KDM5A and TLR activity warrant investigation as combination therapies with ICB agents.

STAT6 correlates with response to immune checkpoint blockade therapy and predicts worse survival in thyroid cancer

2020 ◽  
Vol 14 (11) ◽  
pp. 955-967
Author(s):  
Li Wang ◽  
Shijia Yu ◽  
Yelin Yin ◽  
Ying Hao
Keyword(s):  
Cell Death ◽  
Thyroid Cancer ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Cytotoxic T Lymphocyte ◽  
Prognostic Biomarker ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Signal Transducer

Aim: The signal transducer and activator of transcription (STAT) family has been documented. However, the role of STATs in thyroid cancer was not fully studied. Materials & methods: A survival analysis of STATs was performed. The function modulated by STAT6 was examined. The role of STAT6 in cancer immune infiltrates and immune checkpoint blockade molecules was investigated. Results: Only low STAT6 expression correlated with worse survival. STAT6 is involved in cell cycle, cell adhesion, apoptosis and notch signaling pathways. STAT6 was significantly positively associated with immune infiltration of B cells, CD4+ T cells, neutrophils, macrophages, dendritic cells and the immune checkpoint blockade molecules programmed cell death-ligand 1, programmed cell death-ligand 2 and cytotoxic T-lymphocyte-associated protein 4. Conclusion: STAT6 may act as a prognostic biomarker and provide useful information for immunotherapy in thyroid carcinoma.

scholarly journals Metabolomic adaptations and correlates of survival to immune checkpoint blockade

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Haoxin Li ◽  
Kevin Bullock ◽  
Carino Gurjao ◽  
David Braun ◽  
Sachet A. Shukla ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Resistance Mechanism ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Adaptive Resistance ◽  
Metabolic Monitoring ◽  
Pd1 Blockade ◽  
To Receive ◽  
Cell Death Protein

Abstract Despite remarkable success of immune checkpoint inhibitors, the majority of cancer patients have yet to receive durable benefits. Here, in order to investigate the metabolic alterations in response to immune checkpoint blockade, we comprehensively profile serum metabolites in advanced melanoma and renal cell carcinoma patients treated with nivolumab, an antibody against programmed cell death protein 1 (PD1). We identify serum kynurenine/tryptophan ratio increases as an adaptive resistance mechanism associated with worse overall survival. This advocates for patient stratification and metabolic monitoring in immunotherapy clinical trials including those combining PD1 blockade with indoleamine 2,3-dioxygenase/tryptophan 2,3-dioxygenase   (IDO/TDO) inhibitors.

scholarly journals Impact of Treatment Beyond Progression with Immune Checkpoint Blockade in Hodgkin Lymphoma

2020 ◽  
Vol 25 (6) ◽  
Author(s):  
Reid W. Merryman ◽  
Nicole A. Carreau ◽  
Ranjana H. Advani ◽  
Michael A. Spinner ◽  
Alex F. Herrera ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Treatment Beyond Progression

scholarly journals Integrative Tumor and Immune Cell Multi-omic Analyses Predict Response to Immune Checkpoint Blockade in Melanoma

2020 ◽  
Vol 1 (8) ◽  
pp. 100139
Author(s):  
Valsamo Anagnostou ◽  
Daniel C. Bruhm ◽  
Noushin Niknafs ◽  
James R. White ◽  
Xiaoshan M. Shao ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Cell ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade
Sign in / Sign up

Export Citation Format

Share Document